Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 148 - 148

Published: Jan. 31, 2025

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements our understanding HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines mRNA technology induce broadly neutralizing antibodies, have shown promise. However, efficacy these modest, with best results achieving approximately 30% effectiveness. Ongoing research emphasizes necessity multifaceted strategy overcome obstacles achieve breakthrough development. This review summarizes current approaches utilized further understand create global vaccine. We discuss impact on for other diseases, COVID-19, influenza, Zika virus. Additionally, we highlight specific limitations faced each approach present methods researchers employ challenges. These techniques, which demonstrated preclinical clinical success, advanced field closer ultimate goal developing Leveraging will enable strides combating infectious ultimately improving health outcomes.

Language: Английский

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AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(10), P. 2535 - 2546

Published: Oct. 1, 2023

Abstract The main barrier to HIV cure is a persistent reservoir of latently infected CD4 + T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach target this involves agents reactivate latent proviruses followed by direct clearance expressing induced viral antigens immune effector and immunotherapeutics. We previously showed AZD5582, an antagonist inhibitor apoptosis proteins mimetic the second mitochondrial-derived activator caspases (IAPi/SMACm), induces systemic reversal HIV/SIV latency but with no reduction in size reservoir. In study, we investigated effects AZD5582 combination four SIV Env-specific Rhesus monoclonal antibodies (RhmAbs) ± N-803 (an IL-15 superagonist) SIV-infected, ART-suppressed rhesus macaques. Here confirm efficacy inducing reactivation, demonstrate enhancement when used show total SIV-DNA lymph-node-derived macaques treated RhmAbs. Further exploration therapeutic may contribute goal achieving cure.

Language: Английский

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Antibody prophylaxis may mask subclinical SIV infections in macaques

Nature, Journal Year: 2025, Volume and Issue: 639(8053), P. 205 - 213

Published: Feb. 5, 2025

Broadly neutralizing antibodies (bNAbs) show potential to prevent human immunodeficiency virus (HIV-1) infection in humans1. However, there are limited data on the antibody concentrations required infection. Clinical trials of bNAb prophylaxis have demonstrated partial efficacy2, but sampling frequency typically does not allow precise timing events and concurrent levels. Here, using simian (SIV) rhesus macaques, we that although potent bNAbs can delay onset acute viremia, subclinical infections occur while levels remain high. Serial SIV challenge monkeys given partially fully revealed 'viral blips'-low transient plasma viremia-often serum well above currently accepted protective To understand resulting such blips, performed viral sequencing were serially challenged with genetically barcoded after administration. These analyses showed occurred most animals prophylaxis. 2- 400-fold higher than viremic breakthrough This study demonstrates immunoprophylaxis mask infections, which may affect interpretation prophylactic HIV-1 clinical trials.

Language: Английский

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HIV/AIDS in Indonesia: current treatment landscape, future therapeutic horizons, and herbal approaches

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 14, 2024

HIV/AIDS is still a major worldwide health concern, and Indonesia making efforts to mitigate its effects. Antiretroviral therapy (ARV), which aims decrease viral replication, boost immunological function, lengthen the lifespans of persons living with HIV/AIDS, cornerstone Indonesia’s strategy. The availability ARV has significantly increased, yet problems including stigma requirement for regular medication adherence exist. To address broader needs those affected by lays focus on comprehensive care, includes mental social support, in addition ARV. Data show that, despite progress, there surrounding affects patient outcomes access care. With vigorous research into cutting-edge antiretroviral medications treatment techniques, thriving future therapeutic landscape. goals these programs are increase effectiveness, side effects, treatments. Preventive methods, such as PrEP (pre-exposure prophylaxis), find cure gaining prominence. Notably, management plan heavily relies natural remedies. Patient care incorporates traditional Indonesian medicine, jamu several herbal medicines. Although little scientific proof support effectiveness remedies, complementary alternative therapies frequently employ them manage symptoms promote general wellness. In terms 95-95-95 targets, an effort comply international seeking diagnose 95% HIV-positive individuals, provide sustained diagnosed, achieve suppression recipients. gaps reaching aims, progress being made, part because aforementioned challenges. summary, employs multimodal approach management, cures, continuous treatments, conventional order enhance overall create healthier society, concentrated expanding alternatives, decreasing stigma, improving

Language: Английский

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Dynamic choice HIV prevention with cabotegravir long-acting injectable in rural Uganda and Kenya: a randomised trial extension

The Lancet HIV, Journal Year: 2024, Volume and Issue: 11(11), P. e736 - e745

Published: Oct. 9, 2024

Language: Английский

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Making genome editing a success story in Africa

Nature Biotechnology, Journal Year: 2024, Volume and Issue: 42(4), P. 551 - 554

Published: March 19, 2024

Language: Английский

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Effective and targeted latency reversal in CD4 ⁺ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: March 6, 2024

To date, an affordable, effective treatment for HIV-1 cure remains only a concept with most "latency reversal" agents (LRAs) lacking specificity the latent reservoir and failing in early clinical trials. We assessed latency reversal using multivalent HIV-1-derived virus-like particle (HLP) to treat samples from 32 people living (PLWH) Uganda, US Canada who initiated combined antiretroviral therapy (cART) during chronic infection. Even after 5-20 years on stable cART, HLP could target CD4

Language: Английский

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The Rise of Bacterial G-Quadruplexes in Current Antimicrobial Discovery

ACS Omega, Journal Year: 2024, Volume and Issue: 9(23), P. 24163 - 24180

Published: May 30, 2024

Antimicrobial resistance (AMR) is a silent critical issue that poses several challenges to health systems. While the discovery of novel antibiotics currently stalled and prevalently focused on chemical variations scaffolds available drugs, targets innovative strategies are urgently needed face this global threat. In context, bacterial G-quadruplexes (G4s) emerging as timely profitable for design development antimicrobial agents. Indeed, they expressed in regulatory regions genomes, their modulation has been observed provide effects with translational perspectives context AMR. work, we review current knowledge G4s well by small molecules, including tools techniques suitable these investigations. Finally, critically analyze needs future directions field, focus molecules modulators endowed remarkable drug-likeness.

Language: Английский

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Epitranscriptomic m ⁶ A modifications during reactivation of HIV-1 latency in CD4 ⁺ T cells

mBio, Journal Year: 2024, Volume and Issue: 15(11)

Published: Oct. 7, 2024

ABSTRACT Despite effective antiretroviral therapy reducing HIV-1 viral loads to undetectable levels, the presence of latently infected CD4 + T cells poses a major barrier cure. N 6 -methyladenosine (m A) modification and cellular RNA has functional role in regulating infection. m A can affect its stability, translation, splicing suppresses type-I interferon induction macrophages. However, function latency reactivation remains unknown. We used Jurkat cell line-derived model (J-Lat cells) investigate changes levels response reversal. observed significant increase total upon latent J-Lat cells. This was transient returned steady-state despite continued high gene expression reactivated compared control Upregulation occurred without protein writers or erasers that add remove A, respectively. Knockdown significantly reduced reactivation. Treatment with an writer inhibitor along reduction Furthermore, using A-specific sequencing, we identified RNAs are differentially A-modified during validates these results established primary latency. These show importance IMPORTANCE is important for innate immune responses significance To address this question, study, models latency, sequencing at single-base resolution, assays. demonstrate reversal leads increased modification, correlates dependent on catalytic activity methyltransferase enzyme. also genes reactivation, as well sites within RNA. Our novel findings point toward

Language: Английский

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Novel approaches to enable equitable access to monoclonal antibodies in low- and middle-income countries

PLOS Global Public Health, Journal Year: 2024, Volume and Issue: 4(7), P. e0003418 - e0003418

Published: July 1, 2024

Monoclonal antibodies (mAbs) are revolutionizing management of non-communicable diseases in high-income countries and increasingly being advanced for a range infectious (IDs). However, access to existing mAbs is limited low- middle-income (LMICs), investment developing fit-for-purpose IDs that disproportionately affect LMICs has been limited. Underlying these barriers systemic challenges, including lack commercial incentives target LMIC markets complexity manufacturing regulatory processes. Novel strategies needed overcome mAbs. We outline key areas where new approaches could address barriers, based on multistakeholder consultation March 2023. Three disease-market archetypes identified guide thinking about business models tailored different contexts. New incentivize development ID ensure optimized with product profile cost goods enable use diverse settings. Lessons can be applied from voluntary licensing partnerships have shown success catalysing affordable supply diseases. Technology transfer will expand research capacity sustainable diversified supply. Improved market intelligence, demand aggregation mechanisms, portfolio-based used de-risk establish ecosystem robust technology may reduce data requirements timelines biosimilar approvals. Trailblazer products, coordinated “end-to-end” support funders, demonstrate proof concept pathways accessible across broader LMICs. Research funders; local, regional, global health agencies; and, private sector partners should commit implementing innovative end-to-end equitable

Language: Английский

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